Selectively Cross-Linked Tetra-PEG Hydrogels Provide Control over Mechanical Strength with Minimal Impact on Diffusivity.
Selectively Cross-Linked Tetra-PEG Hydrogels Provide Control over Mechanical Strength with Minimal Impact on Diffusivity.
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DOI：
10.1021/acsbiomaterials.0c01723
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发表时间：
2021-09-13
影响因子：
5.8
通讯作者：
Gentleman E
中科院分区：
文献类型：
--
作者：
Lust ST;Hoogland D;Norman MDA;Kerins C;Omar J;Jowett GM;Yu TTL;Yan Z;Xu JZ;Marciano D;da Silva RMP;Dreiss CA;Lamata P;Shipley RJ;Gentleman E
由聚乙二醇 (PEG) 形成的合成水凝胶广泛用于研究细胞与其细胞外基质的相互作用。这些类似于体内的 3D 环境为组织工程和细胞疗法提供了基础，也为基础生物学问题和疾病建模的研究提供了基础。可以调节 PEG 水凝胶的物理特性，为封装的细胞提供机械信号；然而，改变水凝胶硬度对溶质进出封装细胞的扩散率的影响仅受到有限的关注。这在选择性交联的“四聚乙二醇”水凝胶中尤其如此，其设计限制了网络的不均匀性。在这里，我们结合了理论计算、预测模型和水凝胶膨胀、流变行为和扩散动力学的实验测量，来表征当我们改变聚合物浓度时，四聚乙二醇水凝胶对生物相关尺寸分子扩散的允许性，从而表征水凝胶的机械强度。我们的模型预测水凝胶网格尺寸对模型分子的扩散率几乎没有影响，而是预测扩散速率更高度依赖于溶质尺寸。事实上，我们的模型预测，对于最小的网格尺寸和最大的扩散溶质，水凝胶网格尺寸的变化才开始对从水凝胶中扩散出来的溶质浓度产生不可忽视的影响。表征已知尺寸的异硫氰酸荧光素 (FITC) 标记的葡聚糖分子扩散的实验测量与模型预测非常吻合，表明将聚合物浓度从 2.5% (w/v) 增加到 5% 会产生更硬的凝胶，具有更快的胶凝动力学，而不影响生物相关尺寸的溶质的扩散率，但 10% 水凝胶可以 减缓它们的扩散。我们的研究结果表明，四聚乙二醇水凝胶的硬度可以在生理范围内调节，而不会显着影响溶质进出封装细胞的转运速率。
Synthetic hydrogels formed from poly(ethylene glycol) (PEG) are widely used to study how cells interact with their extracellular matrix. These in vivo-like 3D environments provide a basis for tissue engineering and cell therapies but also for research into fundamental biological questions and disease modeling. The physical properties of PEG hydrogels can be modulated to provide mechanical cues to encapsulated cells; however, the impact of changing hydrogel stiffness on the diffusivity of solutes to and from encapsulated cells has received only limited attention. This is particularly true in selectively cross-linked “tetra-PEG” hydrogels, whose design limits network inhomogeneities. Here, we used a combination of theoretical calculations, predictive modeling, and experimental measurements of hydrogel swelling, rheological behavior, and diffusion kinetics to characterize tetra-PEG hydrogels’ permissiveness to the diffusion of molecules of biologically relevant size as we changed polymer concentration, and thus hydrogel mechanical strength. Our models predict that hydrogel mesh size has little effect on the diffusivity of model molecules and instead predicts that diffusion rates are more highly dependent on solute size. Indeed, our model predicts that changes in hydrogel mesh size only begin to have a non-negligible impact on the concentration of a solute that diffuses out of hydrogels for the smallest mesh sizes and largest diffusing solutes. Experimental measurements characterizing the diffusion of fluorescein isothiocyanate (FITC)-labeled dextran molecules of known size aligned well with modeling predictions and suggest that doubling the polymer concentration from 2.5% (w/v) to 5% produces stiffer gels with faster gelling kinetics without affecting the diffusivity of solutes of biologically relevant size but that 10% hydrogels can slow their diffusion. Our findings provide confidence that the stiffness of tetra-PEG hydrogels can be modulated over a physiological range without significantly impacting the transport rates of solutes to and from encapsulated cells.
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影响因子：
5.5
作者：
Matsunaga, Takuro;Sakai, Takamasa;Shibayama, Mitsuhiro
通讯作者：
Shibayama, Mitsuhiro
影响因子：
16.6
作者：
Ferreira-Gonzalez S;Lu WY;Raven A;Dwyer B;Man TY;O'Duibhir E;Lewis PJS;Campana L;Kendall TJ;Bird TG;Tarrats N;Acosta JC;Boulter L;Forbes SJ
通讯作者：
Forbes SJ
影响因子：
56.9
作者：
Cukierman, E;Pankov, R;Yamada, KM
通讯作者：
Yamada, KM
影响因子：
6.2
作者：
Lutolf, MP;Hubbell, JA
通讯作者：
Hubbell, JA
DOI：
10.1126/science.1171643
发表时间：
2009-06-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Discher DE;Mooney DJ;Zandstra PW
通讯作者：
Zandstra PW